tbuckley/cabot-search huggingface dataset:
Bile acids as modulators of gut microbiota composition and function
Authors: Anaïs B. Larabi, Hugo L. P. Masson, Andreas J. Bäumler
Journal: Gut Microbes (2023)

Changes in the composition of gut-associated microbial communities are associated with many human illnesses, but the factors driving dysbiosis remain incompletely understood. One factor governing the microbiota composition in the gut is bile. Bile acids shape the microbiota composition through their antimicrobial activity and by activating host signaling pathways that maintain gut homeostasis. Although bile acids are host-derived, their functions are integrally linked to bacterial metabolism, which shapes the composition of the intestinal bile acid pool. Conditions that change the size or composition of the bile acid pool can trigger alterations in the microbiota composition that exacerbate inflammation or favor infection with opportunistic pathogens. Therefore, manipulating the composition or size of the bile acid pool might be a promising strategy to remediate dysbiosis.
The multifaceted virulence of adherent-invasive <i>Escherichia coli</i>
Authors: Sarah Mansour, Tahreem Asrar, Wael Elhenawy
Journal: Gut Microbes (2023)

The surge in inflammatory bowel diseases, like Crohn's disease (CD), is alarming. While the role of the gut microbiome in CD development is unresolved, the frequent isolation of adherent-invasive
Oncogenic <i>IDH1</i> Mutation Imparts Therapeutically Targetable Metabolic Dysfunction in Multiple Tumor Types
Authors: Troy M. Robinson, Ross L. Levine
Journal: Cancer Discovery (2023)

Summary: In this issue of Cancer Discovery, Thomas and colleagues leverage mass spectrometry metabolomics, stable isotope labeling, and functional studies to explore metabolic vulnerabilities in cancers harboring mutations in isocitrate dehydrogenase (IDH). The authors present compelling data to support the claim that dysregulated lipid synthesis underpins a synthetic lethal target in cancers with IDH1, but not IDH2, mutations. See related article by Thomas et al., p. 496 (9).
Adherence to Healthy Lifestyle Prior to Infection and Risk of Post–COVID-19 Condition
Authors: Siwen Wang, Yanping Li, Yiyang Yue, Changzheng Yuan, Jae Hee Kang, Jorge E. Chavarro, Shilpa N. Bhupathiraju, Andrea L. Roberts
Journal: JAMA Internal Medicine (2023)

Few modifiable risk factors for post-COVID-19 condition (PCC) have been identified.To investigate the association between healthy lifestyle factors prior to SARS-CoV-2 infection and risk of PCC.In this prospective cohort study, 32 249 women in the Nurses' Health Study II cohort reported preinfection lifestyle habits in 2015 and 2017. Healthy lifestyle factors included healthy body mass index (BMI, 18.5-24.9; calculated as weight in kilograms divided by height in meters squared), never smoking, at least 150 minutes per week of moderate to vigorous physical activity, moderate alcohol intake (5 to 15 g/d), high diet quality (upper 40% of Alternate Healthy Eating Index-2010 score), and adequate sleep (7 to 9 h/d).SARS-CoV-2 infection (confirmed by test) and PCC (at least 4 weeks of symptoms) were self-reported on 7 periodic surveys administered from April 2020 to November 2021. Among participants with SARS-CoV-2 infection, the relative risk (RR) of PCC in association with the number of healthy lifestyle factors (0 to 6) was estimated using Poisson regression and adjusting for demographic factors and comorbidities.A total of 1981 women with a positive SARS-CoV-2 test over 19 months of follow-up were documented. Among those participants, mean age was 64.7 years (SD, 4.6; range, 55-75); 97.4% (n = 1929) were White; and 42.8% (n = 848) were active health care workers. Among these, 871 (44.0%) developed PCC. Healthy lifestyle was associated with lower risk of PCC in a dose-dependent manner. Compared with women without any healthy lifestyle factors, those with 5 to 6 had 49% lower risk (RR, 0.51; 95% CI, 0.33-0.78) of PCC. In a model mutually adjusted for all lifestyle factors, BMI and sleep were independently associated with risk of PCC (BMI, 18.5-24.9 vs others, RR, 0.85; 95% CI, 0.73-1.00, P = .046; sleep, 7-9 h/d vs others, RR, 0.83; 95% CI, 0.72-0.95, P = .008). If these associations were causal, 36.0% of PCC cases would have been prevented if all participants had 5 to 6 healthy lifestyle factors (population attributable risk percentage, 36.0%; 95% CI, 14.1%-52.7%). Results were comparable when PCC was defined as symptoms of at least 2-month duration or having ongoing symptoms at the time of PCC assessment.In this prospective cohort study, pre-infection healthy lifestyle was associated with a substantially lower risk of PCC. Future research should investigate whether lifestyle interventions may reduce risk of developing PCC or mitigate symptoms among individuals with PCC or possibly other postinfection syndromes.
Fast and scarless: Prx1+ fibroblasts turbocharge healing
Authors: Rachel M. Kratofil, Shruti Naik
Journal: The Journal of Experimental Medicine (2023)

Our oral cavity has evolved a capacity for rapid healing without scarring. In this issue of JEM, Ko et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20221350) identify a Prx1+ fibroblast progenitor that drives oral regeneration by summoning pro-healing TGFβ1+ macrophages.
Deprescribing Medications Among Older Adults From End of Hospitalization Through Postacute Care
Authors: Eduard E. Vasilevskis, Avantika Saraf Shah, Emily Kay Hollingsworth, Matthew Stephen Shotwell, Sunil Kripalani, Amanda S. Mixon, Sandra F. Simmons
Journal: JAMA Internal Medicine (2023)

Deprescribing is a promising approach to addressing the burden of polypharmacy. Few studies have initiated comprehensive deprescribing in the hospital setting among older patients requiring ongoing care in a postacute care (PAC) facility.
Enhancing the Management of Metastatic Tumors by Robust Co‐Delivery of 5‐Fluorouracil/MicroRNA‐10b Inhibitor Using EGFR‐Targeted Nanovehicles
Authors: Di Wang, Liwei Wang, Liming Zheng, Jiaxin Chen, Wei Zhang, Wei Zhou, Xiaobo Yang, Lifeng Jiang, Xiaoqiang Jin, Xiaohua Yu, Xin Liu, Heng Chen, Jianbin Xu
Journal: Advanced Healthcare Materials (2023)

Abstract Invasion and metastasis are the leading causes of death of patients with CRC. 5‐Fluorouracil is widely used in clinic practice as the basic chemotherapy drug for CRC. However, it is inefficient in inhibiting tumor metastasis. MicroRNA‐10b is uninvolved in regulating the growth of primary tumors; however, it could induce early tumor metastases and is a key regulator of chemotherapeutic resistance to 5‐FU. A multifunctional nanovehicle that can carry small molecule drugs not only through the hydrophobic pockets of conjugated β ‐cyclodextrin but also through electrostatic interaction between the conjugated peptides and siRNA to target functional genes is previously developed. In this study, a nanovehicle, named GCD, with epithelium growth factor receptor (EGFR)‐targeted characteristics to simultaneously deliver chemotherapeutic and nucleotide drugs to distinct targets in CRC, is employed. These data show that co‐delivery of 5‐FU and anti‐miR‐10b can be effectively applied to targeted therapy of EGFR‐overexpressed CRC, particularly inhibiting the metastasis of CRC. Furthermore, the therapeutic effect of this combination on tumor xenograft models derived from patients with CRC is evaluated. Taken together, this study may provide insights into the inhibition of tumor growth and metastasis simultaneously.
Myocardial Milieu Favors Local Differentiation of Regulatory T Cells
Authors: Murilo Delgobo, Emil Weiß, DiyaaElDin Ashour, Leon Richter, Lisa Popiolkowski, Panagiota Arampatzi, Verena Stangl, Paula Arias-Loza, Encarnita Mariotti-Ferrandiz, Peter P. Rainer, Antoine-Emmanuel Saliba, Burkhard Ludewig, Ulrich Hofmann, Stefan Frantz, Gustavo Campos Ramos
Journal: Circulation Research (2023)

In the past years, several studies investigated how distinct immune cell subsets affects post-myocardial infarction repair. However, whether and how the tissue environment controls these local immune responses has remained poorly understood. We sought to investigate how antigen-specific T-helper cells differentiate under myocardial milieu's influence.
A Splendid New Beginning at the End of a 40-Year Quest: The First KRASG12D Inhibitor in Pancreatic Cancer
Authors: Alexandra Redding, Elda Grabocka
Journal: Cancer Discovery (2023)

Summary: The first KRASG12D inhibitor, MRTX113, leads to regression in multiple mouse models of PDAC as a monotherapy. MRTX113 blocks cancer cell proliferation, induces cancer cell death, and promotes immune infiltration and activation. See related article by Kemp et al., p. 298 (6).
Improving ocular bioavailability of hydrophilic drugs through dynamic covalent complexation
Authors: Jing-jie Wang, Xin-xin Liu, Chen-chen Zhu, Tian-zuo Wang, Si-yu Wang, Yan Liu, Xin-yang Pan, Min-hua Liu, Ding Chen, Ling-li Li, Zhi-min Zhou, Kai-hui Nan
Journal: Journal of Controlled Release (2023)
Black in Cancer: Two Years of Empowering the Next Generation
Authors: Christopher M. Bourne, Henry J. Henderson, Elshaddai White, Julia Morris, Mamadou A. Bah, Rhea Harewood, Stephanie Pierre, Tanimola Martins, Tumisang Ntereke, Briana White, Sigourney Bonner
Journal: Cancer Discovery (2023)

Summary: In the 2 years since the inception of Black in Cancer, we have modeled an action-oriented commitment to improving Black representation across all levels of the cancer spectrum. We reflect on our successes and consider new ways to innovate and inspire the cancer community.
Diagnosis and management of autoimmune hepatitis
Authors: Luigi Muratori, Ansgar W Lohse, Marco Lenzi
Journal: BMJ (2023)

ABSTRACT Autoimmune hepatitis is an inflammatory disease of the liver of unknown cause that may progress to liver cirrhosis and end stage liver failure if diagnosis is overlooked and treatment delayed. The clinical presentation is often that of acute hepatitis, sometimes very severe; less frequently, it can be insidious or completely asymptomatic. The disease can affect people of any age and is more common in women; its incidence and prevalence seem to be on the rise worldwide. An abnormal immune response targeting liver autoantigens and inducing persistent and self-perpetuating liver inflammation is the pathogenic mechanism of the disease. A specific set of autoantibodies, increased IgG concentrations, and histological demonstration of interface hepatitis and periportal necrosis are the diagnostic hallmarks of autoimmune hepatitis. Prompt response to treatment with corticosteroids and other immunomodulatory drugs is almost universal and supports the diagnosis. The aims of treatment are to induce and maintain long term remission of liver inflammation. Treatment can often even reverse liver fibrosis, thus preventing progression to advanced cirrhosis and its complications. Most patients need lifelong maintenance therapy, and repeated follow-up in experienced hands improves the quality of care and quality of life for affected patients.
Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct (Adv. Healthcare Mater. 4/2023)
Authors: Seongchan Kim, You Kyeong Jeong, Chang Sik Cho, SeokHoon Lee, Chang Ho Sohn, Jeong Hun Kim, Youngdo Jeong, Dong Hyun Jo, Sangsu Bae, Hyojin Lee
Journal: Advanced Healthcare Materials (2023)

Genome Editing In article 2201825, Dong Hyun Jo, Sangsu Bae, Hyojin Lee and co-workers develop a novel ribonucleoprotein (RNP) delivery platform, including Cas9 nuclease and base editor, via spongelike structured nanomaterials. This platform increases the delivery efficacy of RNPs in various cells and organs with different genes, and enhances the therapeutic efficiency for tumors, which enables a modular means of in vivo genome editing and other therapeutic purposes.
Patterned Duplex Fabric Based on Genetically Modified Spidroin for Smart Wound Management (Adv. Healthcare Mater. 4/2023)
Authors: Baoyang Lin, Liquan Yuan, Bingbing Gao, Bingfang He
Journal: Advanced Healthcare Materials (2023)

Wound Healing In article 2202213, Bingbing Gao, Bingfang He, and co-workers fabricate a smart patterned DNA double helix (duplex)-like fabric based on genetically modified spider silk protein (PDF-S), which is inspired by soft plant tendrils, and is proposed for diabetic wound treatment.
Bioactive Nonthermal Biocompatible Plasma Enhances Migration on Human Gingival Fibroblasts (Adv. Healthcare Mater. 4/2023)
Authors: Ihn Han, In‐Seok Song, Seung Ah Choi, Taebok Lee, Maksudbek Yusupov, Priyanka Shaw, Annemie Bogaerts, Eun Ha Choi, Jae Jun Ryu
Journal: Advanced Healthcare Materials (2023)

Oral Wound Healing In article 2200527 by Eun Ha Choi, Jae Jun Ryu, and co-workers, nonthermal biocompatible plasma (NBP) stimulates human gingival fibroblast (HGF) cell migration through focal adhesion kinase (FAK) pathway. NBP inhibits colony formation and induces matrix metalloproteinase (MMP) expression, extracellular matrix (ECM) degradation, and subsequent cell migration. NBP plays a role in cell motility to regulate AKT and p21 signals in HGF cells, through actin modification of cytoskeleton.
ZipperCells Exhibit Enhanced Accumulation and Retention at the Site of Myocardial Infarction (Adv. Healthcare Mater. 4/2023)
Authors: Natalie E. Jasiewicz, Kuo‐Ching Mei, Hannah M. Oh, Parth Chansoria, Dylan A. Hendy, Emily E. Bonacquisti, Eric M. Bachelder, Kristy M. Ainslie, Haifeng Yin, Li Qian, Brian C. Jensen, Juliane Nguyen
Journal: Advanced Healthcare Materials (2023)

Amplified Cell Delivery Poor cellular accumulation and retention remain a bottleneck for cardiac repair. In article 2201094 by Juliane Nguyen and co-workers, stem cells decorated with heterodimerizing leucine zippers, termed ZipperCells, are delivered intravenously to form a living drug depot at the infarct site. Non-invasive layer-by-layer dosing amplifies the targetable surface area and stabilizes depot formation for improved cell-based therapy.
3D‐Printed Radiopaque Microdevices with Enhanced Mucoadhesive Geometry for Oral Drug Delivery (Adv. Healthcare Mater. 4/2023)
Authors: Tien‐Jen Chang, Rolf Bech Kjeldsen, Juliane Fjelrad Christfort, Eduard Marzo Vila, Tommy Sonne Alstrøm, Kinga Zór, En‐Te Hwu, Line Hagner Nielsen, Anja Boisen
Journal: Advanced Healthcare Materials (2023)

Gastrointestinal Tracking This cover shows a micro-computed tomography scan image of 3D-printed radiopaque microdevices with an arrow design providing X-ray traceability, as well as potential improved gastrointestinal retention and transit, within oral drug delivery. This work is found in article 2201897 by Tien-Jen Chang, Rolf Bech Kjeldsen, and co-workers.
Towards artificial intelligence-based learning health system for population-level mortality prediction using electrocardiograms
Authors: Weijie Sun, Sunil Vasu Kalmady, Nariman Sepehrvand, Amir Salimi, Yousef Nademi, Kevin Bainey, Justin A. Ezekowitz, Russell Greiner, Abram Hindle, Finlay A. McAlister, Roopinder K. Sandhu, Padma Kaul
Journal: npj Digital Medicine (2023)

The feasibility and value of linking electrocardiogram (ECG) data to longitudinal population-level administrative health data to facilitate the development of a learning healthcare system has not been fully explored. We developed ECG-based machine learning models to predict risk of mortality among patients presenting to an emergency department or hospital for any reason. Using the 12-lead ECG traces and measurements from 1,605,268 ECGs from 748,773 healthcare episodes of 244,077 patients (2007-2020) in Alberta, Canada, we developed and validated ResNet-based Deep Learning (DL) and gradient boosting-based XGBoost (XGB) models to predict 30-day, 1-year, and 5-year mortality. The models for 30-day, 1-year, and 5-year mortality were trained on 146,173, 141,072, and 111,020 patients and evaluated on 97,144, 89,379, and 55,650 patients, respectively. In the evaluation cohort, 7.6%, 17.3%, and 32.9% patients died by 30-days, 1-year, and 5-years, respectively. ResNet models based on ECG traces alone had good-to-excellent performance with area under receiver operating characteristic curve (AUROC) of 0.843 (95% CI: 0.838-0.848), 0.812 (0.808-0.816), and 0.798 (0.792-0.803) for 30-day, 1-year and 5-year prediction, respectively; and were superior to XGB models based on ECG measurements with AUROC of 0.782 (0.776-0.789), 0.784 (0.780-0.788), and 0.746 (0.740-0.751). This study demonstrates the validity of ECG-based DL mortality prediction models at the population-level that can be leveraged for prognostication at point of care.
Crystalline Antibody‐Laden Alginate Particles: A Platform for Enabling High Concentration Subcutaneous Delivery of Antibodies
Authors: Amir Erfani, Jeremy M. Schieferstein, Paul Reichert, Chakravarthy N. Narasimhan, Cinthia Pastuskovas, Vaishali Parab, Denarra Simmons, Xiaoyu Yang, Apoorv Shanker, Paula Hammond, Patrick S. Doyle
Journal: Advanced Healthcare Materials (2023)

Subcutaneous (SC) administration is a desired route for monoclonal antibodies (mAbs). However, formulating mAbs for small injection volumes at high concentrations with suitable stability and injectability is a significant challenge. Here, this work presents a platform technology that combines the stability of crystalline antibodies with injectability and tunability of soft hydrogel particles. Composite alginate hydrogel particles are generated via a gentle centrifugal encapsulation process which avoids use of chemical reactions or an external organic phase. Crystalline suspension of anti-programmed cell death protein 1 (PD-1) antibody (pembrolizumab) is utilized as a model therapeutic antibody. Crystalline forms of the mAb encapsuled in the hydrogel particles lead to stable, high concentration, and injectable formulations. Formulation concentrations as high as 315 mg mL
Employing nanoparticle tracking analysis of salivary neuronal exosomes for early detection of neurodegenerative diseases
Authors: Vaibhav Sharma, Fredrik Nikolajeff, Saroj Kumar
Journal: Translational Neurodegeneration (2023)

Abstract Neurodegenerative diseases are a set of progressive and currently incurable diseases that are primarily caused by neuron degeneration. Neurodegenerative diseases often lead to cognitive impairment and dyskinesias. It is now well recognized that molecular events precede the onset of clinical symptoms by years. Over the past decade, intensive research attempts have been aimed at the early diagnosis of these diseases. Recently, exosomes have been shown to play a pivotal role in the occurrence and progression of many diseases including cancer and neurodegenerative diseases. Additionally, because exosomes can cross the blood–brain barrier, they may serve as a diagnostic tool for neural dysfunction. In this review, we detail the mechanisms and current challenges of these diseases, briefly review the role of exosomes in the progression of neurodegenerative diseases, and propose a novel strategy based on salivary neuronal exosomes and nanoparticle tracking analysis that could be employed for screening the early onset of neurodegenerative diseases.
Advanced Biomaterials for Promoting Endometrial Regeneration
Authors: Zhe Yin, Juan Wang, Wenguo Cui, Chao Tong
Journal: Advanced Healthcare Materials (2023)

Abstract The endometrium, as the innermost structure of the uterine cavity, plays a direct role in the implantation of the fertilized egg, its conception, and the formation of normal menstruation. In recent years, with the increasing rate of uterus‐related surgeries, the damaged endometrium often fails to repair itself to its original state, resulting in a high incidence of menstrual disorders and reduced fertility in women in their reproductive years. Therefore, it is essential to repair the damaged endometrium to reduce menstrual disorders, pregnancy difficulties, and other adverse events. Biomaterials have become an important medical tool for tissue repair due to their excellent biocompatibility, shape plasticity, and functional versatility. Functional biomedical materials play an important role in endometrial repair through rational design, which is expected to fundamentally address the current shortcomings of endometrial repair to maximize repair, maintain female fertility, and solve the problem of medically induced endometrial destruction. This review describes the potential and several aspects of the design, function, and application of different biomedical materials capable of repairing endometrium. In brief, this review provides a comprehensive summary and outlook of biomaterials for endometrial repair.
Endoscopic papillectomy for ampullary lesions in patients with familial adenomatous polyposis compared with sporadic lesions: a propensity score-matched cohort
Authors: Kien Vu Trung, Einas Abou-Ali, Fabrice Caillol, Woo H. Paik, Bertrand Napoleon, Viliam Masaryk, Sophia E. van der Wiel, Enrique Pérez-Cuadrado-Robles, Nicolas Musquer, Asif Halimi, Kevin Soares, Francois R. Souche, Steffen Seyfried, Maria C. Petrone, Stefano Crippa, Tobias Kleemann, David Albers, Tobias J. Weismüller, Ana Dugic, Benjamin Meier, Edris Wedi, Moritz Schiemer, Sara Regner, Sebastien Gaujoux, Marcus Hollenbach
Journal: Endoscopy (2023)

Familial adenomatous polyposis (FAP) is a rare inherited syndrome that predisposes the patient to cancer. Treatment of FAP-related ampullary lesions is challenging and the role of endoscopic papillectomy has not been elucidated. We retrospectively analyzed the outcomes of endoscopic papillectomy in matched cohorts of FAP-related and sporadic ampullary lesions (SALs).This retrospective multicenter study included 1422 endoscopic papillectomy procedures. Propensity score matching including age, sex, comorbidity, histologic subtype, and size was performed. Main outcomes were complete resection (R0), technical success, complications, and recurrence.Propensity score matching identified 202 patients (101 FAP, 101 SAL) with comparable baseline characteristics. FAP patients were mainly asymptomatic (79.2 % [95 %CI 71.2-87.3] vs. 46.5 % [95 %CI 36.6-56.4]); P < 0.001). The initial R0 rate was significantly lower in FAP patients (63.4 % [95 %CI 53.8-72.9] vs. 83.2 % [95 %CI 75.8-90.6]; P = 0.001). After repeated interventions (mean 1.30 per patient), R0 was comparable (FAP 93.1 % [95 %CI 88.0-98.1] vs. SAL 97.0 % [95 %CI 93.7-100]; P = 0.19). Adverse events occurred in 28.7 %. Pancreatitis and bleeding were the most common adverse events in both groups. Severe adverse events were rare (3.5 %). Overall, 21 FAP patients (20.8 % [95 %CI 12.7-28.8]) and 16 SAL patients (15.8 % [95 %CI 8.6-23.1]; P = 0.36) had recurrence. Recurrences occurred later in FAP patients (25 [95 %CI 18.3-31.7] vs. 2 [95 %CI CI 0.06-3.9] months).Endoscopic papillectomy was safe and effective in FAP-related ampullary lesions. Criteria for endoscopic resection of ampullary lesions can be extended to FAP patients. FAP patients have a lifetime risk of relapse even after complete resection, and require long-time surveillance.
One Health and planetary health research: leveraging differences to grow together
Authors: Rafael Ruiz de Castañeda, Jennifer Villers, Carlos A Faerron Guzmán, Turan Eslanloo, Nicole de Paula, Catherine Machalaba, Jakob Zinsstag, Jürg Utzinger, Antoine Flahault, Isabelle Bolon
Journal: The Lancet Planetary Health (2023)
Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study
Authors: Juan Frias, Jenny Chien, Qianyi Zhang, Emmanuel Chigutsa, William Landschulz, Kristen Syring, Paula Wullenweber, Axel Haupt, Christof Kazda
Journal: The Lancet Diabetes & Endocrinology (2023)